Mirtazapine abolishes hyperthermia in an animal model of serotonin syndrome.

Abstract

Serotonin (5-HT) syndrome is a potentially fatal condition associated with various combinations of serotonergic drugs. Hyperthermia is the most serious symptom of this syndrome. Hyperthermia in 5-HT syndrome is reportedly the result of activation of 5-HT(2A) receptors. Mirtazapine is a novel antidepressant and a potent 5-HT(2) receptor antagonistic. Although mirtazapine has been reported to cause 5-HT syndrome, the pharmacological profile of mirtazapine suggests that it improves hyperthermia in 5-HT syndrome. In the present study, we evaluated whether mirtazapine attenuates hyperthermia in a rat model of 5-HT syndrome. This model was induced by administration of tranylcypromine, a nonselective monoamine oxidase inhibitor, and fluoxetine, a selective serotonin reuptake inhibitor. Upon injection of these two drugs, the rectal temperature of the rats increased to over 40 degrees C. Pre- and post-administration of mirtazapine abolishes hyperthermia in this model of 5-HT syndrome. Post-administration of ritanserin, a 5-HT(2A) receptor antagonist, completely inhibited hyperthermia and pre-administration of WAY100635, a 5-HT(1A) receptor antagonist, significantly attenuated the ability of mirtazapine to abolish hyperthermia. The results of the present study suggest that mirtazapine inhibits hyperthermia in an animal model of 5-HT syndrome by blocking the activation of 5-HT(2A) receptors, and that it partly inhibits hyperthermia by activating the 5-HT(1A) receptors. The present study indicates that mirtazapine is unlikely to cause 5-HT syndrome and may be a useful drug for treating this condition.

• Authors: Katsutoshi Shioda, Koichi Nisijima, Tatsuki Yoshino, Satoshi Kato
• Journal: Neuroscience letters (Neurosci Lett) Vol. 482 Issue 3 Pg. 216-9 (Oct 04 2010) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 20655983 (Publication Type: Journal Article)
• Copyright: (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Receptor, Serotonin, 5-HT2A
• Serotonin Antagonists
• Receptor, Serotonin, 5-HT1A
• Mianserin
• Mirtazapine

Topics

• Animals
• Body Temperature (drug effects)
• Disease Models, Animal
• Fever (drug therapy, etiology, metabolism)
• Male
• Mianserin (analogs & derivatives, therapeutic use)
• Mirtazapine
• Rats
• Rats, Wistar
• Receptor, Serotonin, 5-HT1A (metabolism)
• Receptor, Serotonin, 5-HT2A (metabolism)
• Serotonin Antagonists (therapeutic use)
• Serotonin Syndrome (complications, drug therapy, metabolism)